A systematic review on the biochemical threshold of mitochondrial genetic variants.

Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58, P = 0.01, n = 13); however, no correlation was observed in fibroblasts (P = 0.7, n = 9). Our systematic review highlights the need to investigate the biochemical threshold over a wider range of VAFs in disease-relevant cell types to better define the biochemical threshold for specific mtDNA variants.

Prior exposure to antiretroviral therapy among adult patients presenting for HIV treatment initiation or reinitiation in sub-Saharan Africa: a systematic review.

OBJECTIVES: As countries have scaled up access to antiretroviral therapy (ART) for HIV, attrition rates of up to 30% annually have created a large pool of individuals who initiate treatment with prior ART experience. Little is known about the proportion of non-naïve reinitiators within the population presenting for treatment initiation. DESIGN: Systematic review of published articles and abstracts reporting proportions of non-naïve adult patients initiating ART in sub-Saharan Africa. DATA SOURCES: PubMed, Embase Elsevier, Web of Science Core Collection, International AIDS Society conferences, Conference on Retroviruses and Opportunistic Infections conferences. ELIGIBILITY CRITERIA: Clinical trials and observational studies; reporting on adults in sub-Saharan Africa who initiated lifelong ART; published in English between 1 January 2018 and 11 July 2023 and with data collected after January 2016. Initiator self-report, laboratory discernment of antiretroviral metabolites, and viral suppression at initiation or in the medical record were accepted as evidence of prior exposure. DATA EXTRACTION AND SYNTHESIS: We captured study and sample characteristics, proportions with previous ART exposure and the indicator of previous exposure reported. We report results of each eligible study, estimate the risk of bias and identify gaps in the literature. RESULTS: Of 2740 articles, 11 articles describing 12 cohorts contained sufficient information for the review. Proportions of initiators with evidence of prior ART use ranged from 5% (self-report only) to 53% (presence of ART metabolites in hair or blood sample). The vast majority of screened studies did not report naïve/non-naïve status. Metrics used to determine and report non-naïve proportions were inconsistent and difficult to interpret. CONCLUSIONS: The proportion of patients initiating HIV treatment who are truly ART naïve is not well documented. It is likely that 20%-50% of ART patients who present for ART are reinitiators. Standard reporting metrics and diligence in reporting are needed, as is research to understand the reluctance of patients to report prior ART exposure. PROSPERO REGISTRATION NUMBER: CRD42022324136.

The effect of postpartum lifestyle interventions on blood pressure: a systematic literature review.

Postpartum lifestyle modification is recommended to hypertension risk. We conducted a systematic literature review to assess the evidence for postpartum lifestyle interventions to reduce blood pressure. We searched for relevant publications from 2010 through November 2022. Two authors independently conducted article screening and data extraction; a third resolved discrepancies. Ultimately, nine studies met inclusion criteria. Most were randomized controlled trials and had sample sizes <100. In all but one of the eight studies reporting race data, nearly all participants identified as White. None of the studies reported a significant intervention effect on blood pressure. However, most interventions were associated with improvements in other outcomes, such as physical activity. Overall, the evidence for postpartum lifestyle interventions to reduce blood pressure is limited to a handful of studies characterized by small sample sizes and a lack of racial diversity. Additional research with larger samples, more diverse populations, and intermediate outcomes is warranted.

A scoping review of how early-stage knee osteoarthritis has been defined.

BACKGROUND: Early-stage knee osteoarthritis (KOA) classification criteria will enable consistent identification and trial recruitment of individuals with knee osteoarthritis (OA) at an earlier stage of the disease when interventions may be more effective. Toward this goal, we identified how early-stage KOA has been defined in the literature. METHODS: We performed a scoping literature review in PubMed, EMBASE, Cochrane, and Web of Science, including human studies where early-stage KOA was included as a study population or outcome. Extracted data included demographics, symptoms/history, examination, laboratory, imaging, performance-based measures, gross inspection/histopathologic domains, and the components of composite early-stage KOA definitions. RESULTS: Of 6142 articles identified, 211 were included in data synthesis. An early-stage KOA definition was used for study inclusion in 194 studies, to define study outcomes in 11 studies, and in the context of new criteria development or validation in six studies. The element most often used to define early-stage KOA was Kellgren-Lawrence (KL) grade (151 studies, 72%), followed by symptoms (118 studies, 56%), and demographic characteristics (73 studies, 35%); 14 studies (6%) used previously developed early-stage KOA composite criteria. Among studies defining early-stage KOA radiographically, 52 studies defined early-stage KOA by KL grade alone; of these 52, 44 (85%) studies included individuals with KL grade 2 or higher in their definitions. CONCLUSION: Early-stage KOA is variably defined in the published literature. Most studies included KL grades of 2 or higher within their definitions, which reflects established or later-stage OA. These findings underscore the need to develop and validate classification criteria for early-stage KOA.

Meta-Analysis of Randomized Clinical Trials Comparing the Impact of Implantable Loop Recorder Versus Usual Care After Ischemic Stroke for Detection of Atrial Fibrillation and Stroke Risk.

Implantable loop recorder (ILR) is recommended to detect subclinical atrial fibrillation (AF) after cryptogenic stroke; however, the clinical outcomes of this practice is unclear. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate 12-month AF detection, change in oral anticoagulation (OAC), and recurrent stroke in ILR versus usual care after ischemic stroke. We searched Medline, Embase, Web of Science, Cochrane Library for randomized controlled trials comparing ILR with usual care after any ischemic stroke. Primary outcomes were cumulative AF detection and recurrent stroke (ischemic or hemorrhagic) or transient ischemic attack over 12 months. Secondary outcome was OAC initiation. Meta-analysis was performed with Mantel-Haenszel pooled odds ratios (ORs) and random effects models. Of 200 identified articles, 3 trials were included (1,233 participants). Cryptogenic stroke and underlying AF included cryptogenic stroke only, stroke of known cause and underlying-AF included small or large vessel stroke only, and post embolic rhythm detection with implantable vs external monitoring included all ischemic strokes. The 12-month AF detection was 13% in the ILR group and 2.4% in controls. ILR was more likely to detect AF compared with usual care (OR 5.8, 95% confidence interval 3.2 to 10.2). Stroke or transient ischemic attack occurred in 7% with ILR and 9% with usual care (OR 0.8, 95% confidence interval 0.5 to 1.2). In patients with detected AF, 97% and 100% were started on OAC in cryptogenic stroke and underlying AF and post embolic rhythm detection with implantable vs external monitoring, respectively, compared with 68% in stroke of known cause and underlying-AF. In conclusion, ILR was superior to usual care in AF detection, but the relative low incidence of AF and the nondifferential risk of stroke between the ILR and usual care arms may suggest that most patients do not benefit from ILR implantation. Further studies are warranted to understand if patient selection can be improved to increase the diagnostic yield of ILR.

Finding Information Framework: A Tool to Teach Life-Long Learning Skills.

INTRODUCTION: In this age of rapid information expansion, medical education can no longer be taught solely by information acquisition, but rather requires information management and information mastery at both the point of learning as well as at the clinical point of care. We must teach our trainees how to ask, categorize, and answer their own questions-skills required to be a life-long learner. We developed the Finding Information Framework (FIF), a conceptual algorithm as well as web-based tool and app, to guide medical students in asking and categorizing their questions and to link them directly to the most appropriate information resource for their questions. Here we assess the functionality of the FIF following its implementation in the first-year medical school curriculum problem-based learning (PBL) course. METHODS: First-year medical students (n=126) utilized the FIF in their longitudinal problem-based learning course discussion groups and completed an anonymous survey. RESULTS: Qualitative and quantative data suggest that the FIF was easy to use (86.5%), supported the course curriculum (80%), and helped students find relevant information to answer their questions (77%) from trusted reliable resources (70%). Qualitative comments also suggest that the FIF is initially a helpful tool during the PBL course but becomes less useful over time as students become more familiar with resources. CONCLUSION: The FIF assists students in identifying trusted resources and in efficiently and effectively finding answers to questions at the point of learning. These data suggest that students are internalizing the tool's conceptual algorithm over time, reinforcing the teaching of information management and information mastery.

Content and outcomes of narrative medicine programmes: a systematic review of the literature through 2019.

OBJECTIVES: Narrative medicine (NM) incorporates stories into health sciences paradigms as fundamental aspects of the human experience. The aim of this systematic review is to answer the research question: how effective is the implementation and evaluation of NM programmes in academic medicine and health sciences? We documented objectives, content and evaluation outcomes of NM programming to provide recommendations for future narrative-based education. METHODS: We conducted a systematic review of literature published through 2019 using five major databases: PubMed, Embase, PsycINFO, ERIC and MedEdPORTAL. Eligible NM programming included textual analysis/close reading of published literature and creative/reflective writing. Qualifying participants comprised individuals from academic medicine and health sciences disciplines. We reviewed and categorised programme goals, content and evaluation activities to assess participant satisfaction and programme efficacy. Two members of the research team assessed the risk of bias, independently screening records via a two-round, iterative process to reach consensus on eligibility. RESULTS: Of 1569 original citations identified, we selected 55 unique programmes (described in 61 records). In all, 41 (75%) programmes reported a form of evaluation; evaluation methods lacked consistency. Twenty-two programmes used quantitative evaluation (13 well described), and 33 programmes used qualitative evaluation (27 well described). Well-described quantitative evaluations relied on 32 different measures (7 validated) and showed evidence of high participant satisfaction and pre-post improvement in competencies such as relationship-building, empathy, confidence/personal accomplishment, pedagogical skills and clinical skills. An average of 88.3% of participants agreed or strongly agreed that the programme had positive outcomes. Qualitative evaluation identified high participant satisfaction and improvement in competencies such as relationship-building, empathy, perspective-taking/reflection, resilience and burnout detection/mitigation, confidence/personal accomplishment, narrative competence, and ethical inquiry. CONCLUSION: Evaluation suggests that NM programming leads to high participant satisfaction and positive outcomes across various competencies. We suggest best practices and innovative future directions for programme implementation and evaluation.

Analysis of retracted articles in the surgical literature.

BACKGROUND: Retractions of scientific articles represent attempts to correct the literature. Our goal was to examine retracted surgical papers. METHODS: NCBI PubMed database was queried using the search terms "surgery," "surg," or "surgical" and "retracted" or "retraction." Article details were recorded. RESULTS: There were 184 retracted surgical articles identified from 1991 through 2015. Average retraction time was 3.6 years. General (26%), Cardiac (22%), and Orthopedic (10%) surgery were most common. Reasons for retraction were duplication (35.3%), Institutional Review Board violations (18.5%), falsified data (14.7%), data errors (9.8%), author dispute (8.2%), plagiarism (7.6%), copyright violations (2.2%), financial disclosure violations (0.5%), and consent (0.5%). No reason for retraction was given in 8.7% of cases. Median IF was higher for administrative than content-related retraction reasons (3.0 vs. 2.0, P < 0.01). A paywall, requiring a subscription to read, restricted access to 23.4% of retraction notices. CONCLUSIONS: Article retractions occur across all fields of surgery for various reasons, both administrative and content-related. The majority of surgical retraction notices have a reason for retraction listed and do not require payment to read.

A case study: using social tagging to engage students in learning Medical Subject Headings.

In exploring new ways of teaching students how to use Medical Subject Headings (MeSH), librarians at Boston University's Alumni Medical Library (AML) integrated social tagging into their instruction. These activities were incorporated into the two-credit graduate course, "GMS MS 640: Introduction to Biomedical Information," required for all students in the graduate medical science program. Hands-on assignments and in-class exercises enabled librarians to present MeSH and the concept of a controlled vocabulary in a familiar and relevant context for the course's Generation Y student population and provided students the opportunity to actively participate in creating their education. At the conclusion of these activities, students were surveyed regarding the clarity of the presentation of the MeSH vocabulary. Analysis of survey responses indicated that 46% found the concept of MeSH to be the clearest concept presented in the in-class intervention.